气候变化领域集成服务门户(CCPortal): Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex

CCPortal

DOI	10.1073/pnas.2024512118
	Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex
	Xie W.; Wang S.; Wang J.; de la Cruz M.J.; Xu G.; Scaltriti M.; Patel D.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	The Shieldin complex, composed of REV7, SHLD1, SHLD2, and SHLD3, protects DNA double-strand breaks (DSBs) to promote nonhomologous end joining. The AAA+ ATPase TRIP13 remodels Shieldin to regulate DNA repair pathway choice. Here we report crystal structures of human SHLD3–REV7 binary and fused SHLD2–SHLD3–REV7 ternary complexes, revealing that assembly of Shieldin requires fused SHLD2–SHLD3 induced conformational heterodimerization of open (O-REV7) and closed (C-REV7) forms of REV7. We also report the cryogenic electron microscopy (cryo-EM) structures of the ATPγS-bound fused SHLD2–SHLD3–REV7–TRIP13 complexes, uncovering the principles underlying the TRIP13-mediated disassembly mechanism of the Shieldin complex. We demonstrate that the N terminus of REV7 inserts into the central channel of TRIP13, setting the stage for pulling the unfolded N-terminal peptide of C-REV7 through the central TRIP13 hexameric channel. The primary interface involves contacts between the safety-belt segment of C-REV7 and a conserved and negatively charged loop of TRIP13. This process is mediated by ATP hydrolysis-triggered rotatory motions of the TRIP13 ATPase, thereby resulting in the disassembly of the Shieldin complex. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Shieldin assembly; SHLD2–SHLD3–REV7 complex; SHLD2–SHLD3–REV7–TRIP13 complex; SHLD3–REV7 complex; TRIP13-mediated disassembly of Shieldin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180563
作者单位	Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Xie W.,Wang S.,Wang J.,et al. Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex[J],2021,118(8).
APA	Xie W..,Wang S..,Wang J..,de la Cruz M.J..,Xu G..,...&Patel D.J..(2021).Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Xie W.,et al."Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).